The candidate, David W. Kaczka, MD, PhD is an Assistant Professor of Anesthesiology and Critical Care Medicine at the Johns Hopkins University. His long-term career goal is to become an[unreadable] independent scientist conducting translational research in pulmonary physiology. To accomplish this goal,[unreadable] he has developed this proposal outlining a 4-year, multi-disciplinary training program designed to develop[unreadable] the academic career of a biomedical engineer and anesthesiologist. The long-term objective of this project is[unreadable] to develop noninvasive techniques for optimizing mechanical ventilation in patients with acute lung injury[unreadable] (ALI). The hallmark of All is its mechanical heterogeneity, resulting in repetitive intratidal end-expiratory[unreadable] airway closure and end-inspiratory alveolar overdistention during positive pressure ventilation. This causes[unreadable] further lung injury and poor outcomes in patients. Since the nature and degree of .mechanical heterogeneity[unreadable] depend on lung volume, we have hypothesized that ventilating over pressure ranges which minimize[unreadable] heterogeneity can be useful for optimizing therapy in patients and reducing ventilator-associated lung injury[unreadable] (VALI). Thus, the proposed studies will characterize the nature and distribution of regional heterogeneity in[unreadable] injured canine lungs using both functional lung imaging and respiratory mechanical impedance (Zrs).[unreadable] Emphasis will be placed on evaluating the potential of Zrs to provide a real-time, noninvasive assessment of[unreadable] mechanical heterogeneity to allow for the development of individualized ventilation protocols in patients.[unreadable] Specfic Aim 1 will use CT-based 3D image registration to determine how the regional mechanics of the[unreadable] injured lung vary with lung volume. Specific Aim 2 will validate estimates of mechanical heterogeneity[unreadable] inferred from Zrs to those obtained by functional lung imaging. Finally, Specific Aim 3 will develop an[unreadable] optimized, lung protective ventilation strategy based on Zrs, and assess its impact on mechanical[unreadable] heterogeneity and surrogate outcome markers of VALI. Public Health Relevance: By making such[unreadable] measurements in a canine model of ALI, we will evaluate the potential of both CT image registration as well[unreadable] as Zrs to provide specific information regarding the regional mechanical heterogeneity of injured lungs. This[unreadable] will allow for the development of better ventilation protocols in patients with ALI, which will have the potential[unreadable] to minimize the risk of injurious ventilation and reduce its associated mortaility.